Interaction of helminth parasites with the haemostatic system of their vertebrate hosts: a scoping review

Abstract

Helminth parasitoses are among the most prevalent health issues worldwide. Their control depends largely on unravelling host–parasite interactions, including parasitic exploitation of the host haemostatic system. The present study undertakes a scoping review of the research carried out in this field with the aim of unifying and updating concepts. Multiple keywords combined with Boolean operators were employed to design the literature search strategy. Two online databases were used to identify original peer-reviewed articles written in English and published before 1st January 2020 describing molecular interactions between helminth parasites and the host haemostatic system. Relevant data from the selected sources of evidence were extracted and analysed. Ninety-six publications reporting 259 interactions were selected. Fifty-three proteins belonging to 32 species of helminth parasites were involved in interactions with components of the host haemostatic system. Many of these proteins from both parasite and host were conserved among the different interactions identified. Most of these interactions were related to the inhibition of the coagulation system and the activation of fibrinolysis. This was associated mainly with a potential of parasites to reduce the formation of blood clots in the host and attributed to biological processes, such as parasite nutrition, survival, invasion, evasion and migration or the appearance of pathological mechanisms in the host. A wide range of helminth parasites have developed similar strategies to exploit the haemostatic system of their hosts, which could be regarded as an evolutionary conserved mechanism that could confer benefits to parasites in terms of survival and establishment in their vertebrate hosts.

Fasciola hepaticajuveniles interact with the host fibrinolytic system as a potential early-stage invasion mechanism

“…CC-BY 4.0 International license perpetuity. It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2022. ; https://doi.org/10.1101/2022.11.07.515559 doi: bioRxiv preprint 20 mechanisms poses great difficulties to confront this interaction through classic control and therapeutic strategies (13).…”

“…This is precisely what we observe in this study: the use of proteins with highly divergent biological functions for PLG binding/plasmin activation purposes (see Figure 6A for a GO annotation of the potential PLG-binding proteins identified by 2D-MS), which reinforces the notion that the interaction between FhNEJ and the fibrinolytic system of the host ensures parasite fitness and thus represents an essential mechanism for parasite survival inside the mammalian organism. Unfortunately, the fact that FhNEJ interact with the host fibrinolytic system via such redundant mechanisms poses great difficulties to confront this interaction through classic control and therapeutic strategies (13).…”

“…The interaction between parasites and the fibrinolytic system of the host has been demonstrated in very diverse organisms, including bacteria, fungi and parasites, and proposed to be beneficial for parasite survival and migration inside the vertebrate host and also a mechanism of immune evasion (13)(14)(15)30). Adult flukes of F. hepatica express and secrete proteins that are capable of interacting with PLG and stimulate its conversion to the effector protease, plasmin (16,17), and we hypothesized that this interaction may also occur in the juvenile stages of the parasite and serve as a mechanism for FhNEJ to overcome the intestinal wall and initiate tissue migration throughout the mammalian host.…”

“…Although t-PA expression is mostly restricted to the vascular endothelium, u-PA is expressed in different tissues across the organism and can therefore stimulate plasmin generation in the extravascular space (19). This, in conjunction with the wide array of plasmin substrates, including ECM components (19), matrix metalloproteinases (20) and the C3 and C5 complement molecules (21), explains why host-derived plasmin could be a highly valuable tool for parasites to migrate through the mammalian organism, modulate immune responses and overall increase their chances of survival within their definitive hosts (13)(14)(15). The aim of the present work is to investigate whether FhNEJ interact with the fibrinolytic system and promote plasmin generation at their surface as a potential mechanism to facilitate trans- intestinal migration.…”

“…In addition to their endogenous repertoire of proteases, it is possible that FhNEJ co-opt proteolytic functions of the host in order to migrate more efficiently in terms of energy expenditure. A paradigmatic example of exploitation of host resources is the interaction between parasites and plasminogen (PLG), the central pro-enzyme of the mammalian fibrinolytic system (13–15), which has been described in adult F. hepatica via the secretion of PLG-binding proteins and proposed to be a mechanism of survival inside the biliary ducts (16,17). PLG is converted into its active form, plasmin, by the serine proteases tissue-type or urokinase-type plasminogen activators (t-PA and u-PA, respectively).…”